This research was primarily aimed at assessing comparatively the potential carcinogenic risk of low level tritium internal irradiation, either from tritiated water or tritiated precursors of DNA or RNA, in C57 Black/6 M mice, in relationship with differential incorporation into various molecular sites. A preliminary extensive study of the spontaneous tumorigenesis in control unexposed mice revealed an extremely high frequency of neoplasms occurring in animals observed over a maximum lifespan extended up to about 1,200 days. Hence the definition of the basic tumor spectrum in C57 Black/6 M mice became a primary goal as low level tritium irradiation appeared to trigger a modulation of the carcinogenic process mainly evidenced by significant time shifts of specific tumor peak frequencies or by slight variations in the induction of specific tumor types. As a tritium is predominantly incorporated into the cell nucleus, the associated carcinogenic risk might conceivably bear some distinct relationship to the genetic risk, especially after cumulative damage has been inflicted over successive generations. In an attempt to evaluate a possible interaction of cumulative genetic injury and carcinogenic potency following low level tritium irradiation, propagation of three sublines was carried out through mating of sibling couples whose male parent was, at weaning time, either injected with tritiated thymidine or exposed for 35 days to tritiated drinking water or exposed to natural water. At this time, 16 successive generations have been produced. It is planned to carry the experiment to the 20th generation, with the aim of assessing any variation in the reproductive fitness, in the occurrence of dominant lethal mutations, or any significant shift from the basic tumor spectrum at the 10th and 20th generation.